Luca Prosperini

One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis

Background and purpose:  To define the predictive value of clinical and magnetic resonance imaging (MRI) characteristics in identifying relapsing‐remitting multiple sclerosis (RR‐MS) patients with sustained disability progression during interferon beta (IFNB) treatment.

Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.

Objective. To evaluate the effectiveness of a home-based rehabilitation of balance using the Nintendo Wii Balance Board System (WBBS) in patients affected by multiple sclerosis (MS). Methods. In this 24-week, randomized, 2-period crossover pilot study, 36 patients having an objective balance disorder were randomly assigned in a 1:1 ratio to 2 counterbalanced arms. Group A started a 12-week period of home-based WBBS training followed by a 12-week period without any intervention; group B received the treatment in reverse order. As endpoints, we considered the mean difference (compared with baseline) in force platform measures (ie, the displacement of body center of pressure in 30 seconds), 4-step square test (FSST), 25-foot timed walking test (25-FWT), and 29-item MS Impact Scale (MSIS-29), as evaluated after 12 weeks and at the end of the 24-week study period. Results. The 2 groups did not differ in baseline characteristics. Repeated-measures analyses of variance showed significant time × treatment effects, indicating that WBBS was effective in ameliorating force platform measures (F = 4.608, P = .016), FSST (F = 3.745, P = .034), 25-FWT (F = 3.339, P = .048), and MSIS-29 (F = 4.282, P = .023). Five adverse events attributable to the WBSS training (knee or low back pain) were recorded, but only 1 patient had to retire from the study. Conclusion. A home-based WBBS training might potentially provide an effective, engaging, balance rehabilitation solution for people with MS. However, the risk of WBBS training-related injuries should be carefully balanced with benefits. Further studies, including cost-effectiveness analyses, are warranted to establish whether WBBS may be useful in the home setting.

The diagnostic accuracy of static posturography in predicting accidental falls in people with multiple sclerosis.

Background. Quantitative posturography has been reported as a reliable tool to measure balance in people with multiple sclerosis (MS). However, data on its diagnostic accuracy in predicting the occurrence of falls are lacking. Objective. To determine sensitivity, specificity, predictive values, and accuracy of posturography in detecting falls in MS subjects over a 3-month follow-up period. Methods. One hundred consecutive patients with MS were tested by the Berg Balance Scale (BBS) and by static posturography on a monoaxial platform. Participants recorded the occurrence of accidental falls for the next 3 months. Abnormal cutoff values for static standing balance measures were set at 2 standard deviations above the mean values obtained from 50 healthy controls (HC). The diagnostic accuracy of the BBS and static posturography was analyzed with respect to the prospectively collected data on the occurrence of falls. Results. Posturometric measures in participants with MS were significantly worse than in HC (all P values <.0001); however, only the center of pressure (COP) path with open eyes condition had substantial test–retest reliability. Static posturography was more sensitive (88% vs 37%) and accurate (75% vs 63%), but slightly less specific (67% vs 81%), than the BBS in predicting accidental falls. A logistic regression analysis revealed that the worse the COP path, the greater the risk for accidental falls (odds ratio = 1.08; P < .0001), even after adjusting for sex, age, disease duration, body mass index, MS subtype, Expanded Disability Status Scale, and BBS score. Conclusion. The COP path measurement in static position is a sensitive and accurate tool to identify people with MS who are at risk of accidental falls.

Early physiotherapy after injection of botulinum toxin increases the beneficial effects on spasticity in patients with multiple sclerosis

Objective : To determine whether additional physiotherapy increases botulinum toxin type A effects in reducing spasticity in patients with multiple sclerosis. Design : A single-blind, randomized, controlled pilot trial with a 12-week study period. Subjects : Thirty-eight patients with progressive multiple sclerosis affected by focal spasticity and who were observed at the Multiple Sclerosis Centre operating in the S. Andrea Hospital in Rome. Interventions : For intervention all patients received botulinum toxin type A; the treatment group also received additional physiotherapy to optimize management through passive or active exercise and stretching regimens. Main measures : To measure objective and subjective level of spasticity, patients were assessed at baseline, 2, 4 and 12 weeks post treatment by Modified Ashworth Scale and visual analogue scale. Results : When compared with the control group, we found a significant decrease of spasticity by Modified Ashworth Scale (P < 0.01 by t-test) in the treatment group at week 2 (2.73 versus 3.22), week 4 (2.64 versus 3.33) and week 12 (2.68 versus 3.33). The mean (%) difference in Modified Ashworth Scale score between baseline and the end of follow-up was —0.95 (26.1) in the treatment group and —0.28 (7.7) in the control group (P < 0.01). The combined treatment proved also to be more effective by visual analogue scale (P < 0.01) at week 4 (6.95 versus 5.50) and at week 12 (7.86 versus 6.56) but not at week 2 (5.18 versus 5.50; P = 0.41). Conclusions : Our data suggest that physiotherapy in combination with botulinum toxin type A injection can improve overall response to botulinum toxin.

Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis

Objective: To evaluate whether an escalation approach was more effective in suppressing clinical and magnetic resonance imaging (MRI) activity than switching among immunomodulators in relapsing–remitting multiple sclerosis (RRMS) patients. Methods: In this post-marketing, prospective, observational study in two Italian multiple sclerosis (MS) centres, a total of 285 RRMS patients who failed a first-line treatment with interferon beta (IFNβ) or glatiramer acetate (GA) were considered. Patients were subdivided according to the strategy adopted after the failure (defined as the occurrence of ≥2 relapses or 1 relapse with residual disability): the switching (SWI) group, i.e. those switched among different IFNβ formulations, or from IFNβ to GA and vice versa; and the escalating (ESC) group, i.e. those escalated to natalizumab. Proportions of patients free from different types of disease activity (relapses, sustained disability progression, new active lesions on MRI, or a combination of them) were calculated at 12 and 24 months. Since patients were not randomized to treatment group, propensity score (PS)-adjusted Cox regression models were built to control for several potential confounders. Results: At 12 months there were no differences between the two groups in proportions of patients free from relapse, disability progression, MRI activity, and combined activity. After 24 months we observed greater proportions of patients in the ESC than SWI group free from relapse (p < 0.0001), disability progression (p = 0.0045), MRI activity (p = 0.0003), and combined activity (p < 0.0001). PS-adjusted models confirmed these findings, with hazard ratios ranging from 0.38 to 0.56 favours the ESC group. Conclusion: We suggest that an escalation to natalizumab is more effective than switching among immunomodulators in RRMS patients who failed a first-line treatment.

Assessing the Correlation between Grey and White Matter Damage with Motor and Cognitive Impairment in Multiple Sclerosis Patients

Background Multiple sclerosis (MS) is characterized by demyelinating and degenerative processes within the central nervous system. Unlike conventional MRI,new advanced imaging techniques improve pathological specificity and better highlight the relationship between anatomical damage and clinical impairment. Objective To investigate the relationship between clinical disability and both grey (GM) and white matter (WM) regional damage in MS patients. Methods Thirty-six relapsing remitting-MS patients and 25 sex- and age-matched controls were enrolled. All patients were clinically evaluated by the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite (MSFC) scale, which includes the 9-hole peg test (9HPT), the timed 25-feet walking test (T25FW) and the paced auditory serial addition test (PASAT). All subjects were imaged by a 3.0 T scanner: dual-echo fast spin-echo, 3DT1-weighted and diffusion-tensor imaging (DTI) sequences were acquired. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses were run for regional GM and WM assessment, respectively. T2 lesion volumes were also calculated, by using a semi-automated technique. Results Brain volumetric assessment of GM and DTI measures revealed significant differences between patients and controls. In patients, different measures of WM damage correlated each-other (p<0.0001), whereas none of them correlated with GM volume. In patients, focal GM atrophy and widespread WM damage significantly correlated with clinical measures. In particular, VBM analysis revealed a significant correlation (p<0.05) between GM volume and 9HPT in cerebellum and between GM volume and PASAT in orbito-frontal cortex. TBSS showed significant correlations between DTI metrics with 9HPT and PASAT scores in many WM bundles (p<0.05), including corpus callosum, internal capsule, posterior thalamic radiations, cerebral peduncles. Conclusions Selective GM atrophy and widespread WM tracts damage are associated with functional impairment of upper-limb motion and cognition. The combined analysis of volumetric and DTI data may help to better understand structural alterations underlying physical and cognitive dysfunction in MS.

The relationship between infratentorial lesions, balance deficit and accidental falls in multiple sclerosis

OBJECTIVE The role of static posturography and magnetic resonance imaging (MRI) in identifying patients at high risk of falls was investigated. Relationships between static posturography measures and MRI metrics were also investigated. METHODS A total of 31 ambulatory MS patients (EDSS ranging from 2.0 to 5.0) with a predominant balance disorder were recruited. Each patient underwent a static posturography with a monoaxial platform and a conventional 1.5 T brain MRI scan. Measurements of T1-hypointense and T2-hyperintense lesion volumes (LVs), focusing on lesions selectively located at infratentorial levels, were performed by two operators unaware of clinical data. The self-reported number of falls in the previous 6 months was considered as the main outcome measure. RESULTS Fourteen (45%) patients reported 1 or more falls over the past 6 months. When compared to non-faller patients, they had a higher EDSS score, poorer static standing balance, and greater brainstem and middle cerebellar peduncle (MCP) T2-LVs. A strength correlation between brainstem T2-LV and impaired static standing balance in an open eye condition was also found. In the multivariate analysis, the variables more strictly associated with recurrent falls were greater T2-LV at the MCP (beta: 6.2; p=0.01) and brainstem (beta: 5.8; p=0.001) levels, and a wider displacement of the body center of pressure in the closed eye condition (beta: 0.02; p=0.03). CONCLUSION Our data suggests that the damage of specific infratentorial areas negatively affect the static standing balance and may predispose MS patients to accidental falls. These findings might contribute in selecting patients requiring a proper rehabilitation intervention program.

Natalizumab treatment in pediatric multiple sclerosis: A case report

Pediatric multiple sclerosis (MS) with manifestations before 16 years of age occurs in 0.4-10.5% of whole MS population. The initial course of the disease is relapsing-remitting with a relapse rate generally higher than that of adults, less than 3% have a primary progressive form. Some recent reports have shown that Interferon beta (IFNbeta) has a strong effect in reducing the relapse rate in children with MS and is well tolerated. We report a 12-year-old girl with MS and a high relapse rate from the onset. Frequent magnetic resonance imaging (MRI) detected persisting inflammatory activity and increase of lesion burden. She continued to present acute relapses and progression of disability in spite of a treatment with IFNbeta-1a at different dosages and the addition of pulse IV steroid treatment. Then, we opted for Natalizumab treatment, recently approved as a monotherapy for patients with MS who experienced inadequate response to other disease modifying therapies and never used till now in pediatric MS. Our patient showed a complete response to Natalizumab with clinical and MRI suppression of disease activity.

Pulse monthly steroids during an elective interruption of natalizumab: A post-marketing study

Background and purpose:  Temporary discontinuation of natalizumab is sometimes considered as the observed risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS). However, interruption of natalizumab may result in a re‐start of disease activity.

A systematic review of factors associated with accidental falls in people with multiple sclerosis: a meta-analytic approach:

Objective: To determine whether there are demographic, clinical, and instrumental variables useful to detect fall status of patients with multiple sclerosis. Data sources: PubMed and the Cochrane Library. Review methods: Eligible studies were identified by two independent investigators. Only studies having a clear distinction between fallers and non-fallers were included and meta-analysed. Odds ratios (ORs) and standard mean differences (SMDs) were calculated and pooled using fixed effect models. Results: Among 115 screened articles, 15 fulfilled criteria for meta-analyses, with a total of 2425 patients included. Proportion of fallers may vary from 30% to 63% in a time frame from 1 to 12 months. No significant publication bias was found, even though 12/15 studies relied on retrospective reports of falls, thus introducing recall biases. Risk factors for falls varied across studies, owing to heterogeneity of populations included and clinical instruments used. The meta-analytic approach found that, compared with non-fallers, fallers had longer disease duration (SMD = 0.14, p = 0.02), progressive course of disease (OR = 2.02, p < 0.0001), assistive device for walking (OR = 3.16, p < 0.0001), greater overall disability level (SMD = 0.74, p < 0.0001), slower walking speed (SMD = 0.45, p = 0.0005), and worse performances in balance tests (Berg Balance Scale: SMD = −0.48, p = 0.002; Timed up-and-go test, SMD = 0.31, p = 0.04), and force-platform measures (postural sway) with eyes opened (SMD = 0.71, p = 0.006) and closed (SMD = 0.83, p = 0.01), respectively. Conclusion: Elucidations regarding risk factors for accidental falls in patients with multiple sclerosis (PwMs) are provided here, with worse disability score, progressive course, use of walking aid, and poorer performances in static and dynamic balance tests strongly associated with fall status.